Human leukocyte antigen (HLA) DR15 is associated with reduced incidence of acute GVHD in HLA-matched allogeneic transplantation but does not impact chronic GVHD incidence

Abstract

The DR15 allele at the HLA DRB1 locus is a marker for immune-mediated bone marrow failure syndromes. We hypothesized that HLA DR15 plays a role in T-cell interactions with hematopoiesis and investigated the role of HLA DR15 on graftversus-host disease (GVHD) and graftversus-leukemia effects in HLA-matched allogeneic blood or marrow transplantation (BMT) performed for myeloid malignancies. We performed a retrospective analysis of 119 consecutive related and 48 consecutive unrelated allogeneic BMT for myeloid malignancies treated between 1991 and 2005 to investigate the influence of HLA DR15 on overall survival (OS), progression-free survival (PFS), and incidence of grades II to IV acute GVHD. HLA DR15 was determined by either molecular (n ‫؍‬ 108) or serologic (n ‫؍‬ 59) methods. The incidence of HLA DR15 was similar to the general white population (35/167 ‫؍‬ 21%). There were no significant differences in transplantation characteristics between the HLA DR15-positive and -negative groups. There was no significant difference in chronic GVHD, OS, or PFS between the HLA DR15-positive versus-negative groups in any disease or donor relation subgroups. The HLA DR15-positive group experienced a significantly lower incidence of acute GVHD grades II to IV: 23% versus 42% (P ‫؍‬ .041). These results suggest that HLA DR15 reduces the risk of acute GVHD. (Blood.

The impact of frequent HLA haplotypes in high linkage disequilibrium on donor search and clinical outcome after unrelated haematopoietic SCT

“…Furthermore, HLA-DR15-positive patients transplanted from HLA-matched donors have shown a reduced incidence of aGVHD for HLA-DR15-positive patients transplanted from HLA-matched donors. 38 The most frequent five-locus allele level-typed HLA haplotypes found in the Dutch population were comparable to other Northwest European populations. The sample population was in Hardy-Weinberg equilibrium; therefore, we conclude the sample was free from selection bias and was large enough to estimate reliable haplotypes from.…”

Association between human leukocyte antigens and graft-versus-host disease occurrence after allogenic hematopoietic stem cell transplantation

“…4 However, there is a hypothesis that immunodominant myeloid antigens are preferentially presented by HLA-DR15, thus suggesting that this allele has an important role in relation to acute GVHD development.…”

“…[3][4][5][6][7][8][9][10][11][18][19][20][21][22][23][24] Our analysis investigated the role of class I and II HLA variants on GVHD development in a population of 176 patients, and suggests that these were determinants for acute and chronic GVHD in allogenic HSCT patients with an HLA-identical sibling donor. HLA-A26 (a split of HLA-A10) was associated with higher risk of acute GVHD, in agreement with previous studies.…”

“…9 According to Battiwalla et al, there was no significant difference in the two groups, regarding chronic GVHD incidence or severity. 4 The differences between various HLA variants and their correlations with the risk of GVHD in different centers and countries may be due to differences in ethnicity between populations.…”

“…Identifying GVHD risk factors may help to reduce its incidence and severity. Previous reports have suggested that particular HLA system factors have an impact on GVHD [3][4][5][6][7][8][9][10][11] and give rise to a reduced relapse rate and improved survival after HSCT. 12 HLA molecules are the most important immunogenic proteins contributing towards the intensity of the GVHD reaction.…”